Extracellular DNA-induced antimicrobial peptide resistance mechanisms in Pseudomonas aeruginosa

ABSTRACT Pseudomonas aeruginosa is an important opportunistic pathogen that causes infections that can be extremely difficult to treat due to its high intrinsic antibiotic resistance and broad repertoire of virulence factors, both of which are highly regulated. It is demonstrated here that the psrA gene, encoding a transcriptional regulator, was upregulated in response to subinhibitory concentrations of cationic antimicrobial peptides. Compared to the wild type and the complemented mutant, a P. aeruginosa PAO1 psrA::Tn5 mutant displayed intrinsic supersusceptibility to polymyxin B, a last-resort antimicrobial used against multidrug-resistant infections, and the bovine neutrophil antimicrobial peptide indolicidin; this supersusceptibility phenotype correlated with increased outer membrane permeabilization by these agents. The psrA mutant was also defective in simple biofilm formation, rapid attachment, and swarming motility, all of which could be complemented by the cloned psrA gene. The role of PsrA in global gene regulation was studied by comparing the psrA mutant to the wild type by microarray analysis, demonstrating that 178 genes were up- or downregulated ≥2-fold (P ≤ 0.05). Dysregulated genes included those encoding certain known PsrA targets, those encoding the type III secretion apparatus and effectors, adhesion and motility genes, and a variety of metabolic, energy metabolism, and outer membrane permeability genes. This suggests that PsrA might be a key regulator of antimicrobial peptide resistance and virulence.

Download Full-text

Cationic antimicrobial peptide resistance mechanisms of streptococcal pathogens

Biochimica et Biophysica Acta (BBA) - Biomembranes ◽

10.1016/j.bbamem.2015.02.010 ◽

2015 ◽

Vol 1848 (11) ◽

pp. 3047-3054 ◽

Cited By ~ 47

Author(s):

Christopher N. LaRock ◽

Victor Nizet

Keyword(s):

Antimicrobial Peptide ◽

Resistance Mechanisms ◽

Cationic Antimicrobial Peptide ◽

Antimicrobial Peptide Resistance

Download Full-text

Antimicrobial Peptide Resistance Mechanisms of Human Bacterial Pathogens

Current Issues in Molecular Biology ◽

10.21775/cimb.008.011 ◽

2006 ◽

Cited By ~ 3

Keyword(s):

Antimicrobial Peptide ◽

Bacterial Pathogens ◽

Resistance Mechanisms ◽

Antimicrobial Peptide Resistance

Download Full-text

The evolution of antimicrobial peptide resistance in Pseudomonas aeruginosa is shaped by strong epistatic interactions

Nature Communications ◽

10.1038/ncomms13002 ◽

2016 ◽

Vol 7 (1) ◽

Cited By ~ 56

Author(s):

Nicholas Jochumsen ◽

Rasmus L. Marvig ◽

Søren Damkiær ◽

Rune Lyngklip Jensen ◽

Wilhelm Paulander ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Antimicrobial Peptide ◽

Epistatic Interactions ◽

Antimicrobial Peptide Resistance

Download Full-text

Clinical Implications of Pseudomonas aeruginosa: Antibiotic Resistance, Phage & Antimicrobial Peptide Therapy

Proceedings of the Singapore National Academy of Science ◽

10.1142/s2591722619400076 ◽

2019 ◽

Vol 13 (01) ◽

pp. 65-86 ◽

Cited By ~ 3

Author(s):

Wee Siang Lim ◽

Pooi Leng Ho ◽

Sam Fong-Yau Li ◽

Dave Siak-Wei Ow

Keyword(s):

Pseudomonas Aeruginosa ◽

Antibiotic Resistance ◽

Antimicrobial Peptide ◽

Major Gene ◽

Opportunistic Pathogen ◽

Resistance Mechanisms ◽

Clinical Implications ◽

Variant Form ◽

Alternative Treatment Strategy ◽

Conventional Antibiotics

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen that is found ubiquitously in the environment. It is also the cause of nosocomial infections, which affects patients with cystic fibrosis (CF) and cathether-related infections. Treatment and eradication of P. aeruginosa is an uphill task as it has already developed resistance to many commonly used antibiotics. Some of the resistance mechanisms that P. aeruginosa employ are having low cell wall permeability, developing efflux system to pump antibiotics out, producing enzymes to inactivate antibiotics, modifying antibiotic targets, forming biofilm as a protection layer against antibiotics, and turning into more pathogenic small colony variant form. In addition, P. aeruginosa uses a host of signaling mechanisms, such as secretion system and quorum sensing, to aid its virulence. With numerous resistance mechanisms developed against conventional antibiotics, new strategies to treat P. aeruginosa infection are required. Bacteriophages such as natural bacteria viruses and studies have suggested that they can be used as an alternative to antibiotics for treatment against P. aeruginosa infections. However, phage therapy also shares the same problem with that of antibiotics, i.e., the development and emergence of bacteria resistance by masking or altering surface recognition features, inhibiting phage DNA injection and employing abortive infection (Abi) system. Another alternative treatment strategy is to use antimicrobial peptides, which are small cationic peptides that are naturally found in most organisms’ immune system. These peptides disrupt cell membrane and key cellular processes, which requires major gene alteration if evasion is needed. Hence, lowering likelihood of resistance development. This paper aims to review our current understanding of the clinical implications of P. aeruginosa infections, the mechanisms of antibiotic resistance, phage-inspired and antimicrobial peptide approaches for treatment of P. aeruginosa infections.

Download Full-text

Bis-(3′-5′)-Cyclic Dimeric GMP Regulates Antimicrobial Peptide Resistance in Pseudomonas aeruginosa

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02499-12 ◽

2013 ◽

Vol 57 (5) ◽

pp. 2066-2075 ◽

Cited By ~ 61

Author(s):

Song Lin Chua ◽

Sean Yang-Yi Tan ◽

Morten Theil Rybtke ◽

Yicai Chen ◽

Scott A. Rice ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Antimicrobial Peptide ◽

Second Messenger ◽

Intracellular Level ◽

Planktonic Cells ◽

Proteomics Analysis ◽

Content Type ◽

Antimicrobial Peptide Resistance ◽

Dispersed Cells

ABSTRACTBis-(3′-5′)-cyclic dimeric GMP (c-di-GMP) is an intracellular second messenger that controls the lifestyles of many bacteria. A high intracellular level of c-di-GMP induces a biofilm lifestyle, whereas a low intracellular level of c-di-GMP stimulates dispersal of biofilms and promotes a planktonic lifestyle. Here, we used the expression of different reporters to show that planktonic cells, biofilm cells, and cells dispersed from biofilms (DCells) had distinct intracellular c-di-GMP levels. Proteomics analysis showed that the low intracellular c-di-GMP level of DCells induced the expression of proteins required for the virulence and development of antimicrobial peptide resistance inPseudomonas aeruginosa. In accordance with this,P. aeruginosacells with low c-di-GMP levels were found to be more resistant to colistin thanP. aeruginosacells with high c-di-GMP levels. This finding contradicts the current dogma stating that dispersed cells are inevitably more susceptible to antibiotics than their sessile counterparts.

Download Full-text

Faculty Opinions recommendation of Extracellular DNA chelates cations and induces antibiotic resistance in Pseudomonas aeruginosa biofilms.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1147872.604962 ◽

2009 ◽

Author(s):

Leo Eberl

Keyword(s):

Pseudomonas Aeruginosa ◽

Antibiotic Resistance ◽

Extracellular Dna

Download Full-text

Potential Antimicrobial Peptides Elucidation From The Marine Bacteria

Cardiovascular & Hematological Agents in Medicinal Chemistry ◽

10.2174/1871525718666200512074400 ◽

2020 ◽

Vol 18 ◽

Cited By ~ 1

Author(s):

Adyasa Barik ◽

Pandiyan Rajesh ◽

Manthiram Malathi ◽

Vellaisamy Balasubramanian

Keyword(s):

Antimicrobial Peptide ◽

Marine Bacteria ◽

Unnatural Amino Acids ◽

Wide Spectrum ◽

Drug Resistant ◽

Medical Field ◽

The World ◽

Pathogenic Microbes ◽

Antimicrobial Peptide Resistance ◽

Significant Attention

: In recent years, over use of antibiotics has been raising its head to a serious problem all around the world as pathogens become drug resistant and create challenges to the medical field. This failure of most potent antibiotics that kill pathogens increases the thirst for research to look further way of killing pathogens. It has been led to the findings of antimicrobial peptide which is the most potent peptide to destroy pathogens. This review gives special emphasis to the usage of marine bacteria and other microorganisms for antimicrobial peptide (AMP) which are eco friendly as well as a developing class of natural and synthetic peptides with a wide spectrum of targets to pathogenic microbes. Consequently, a significant attention has been paid mainly to (i) the structure and types of anti microbial peptides and (ii) mode of action and mechanism of antimicrobial peptide resistance to pathogens. In addition to this, the designing of AMPs has been analysed thoroughly for reducing toxicity and developing better potent AMP. It has been done by the modified unnatural amino acids by amidation to target the control of biofilm and persister cell.

Download Full-text